amphotericin B deoxycholate

Action and Spectrum

Actions and Spectrum: 

• amphotericin B is a broad-spectrum antifungal medication used to treat severe and potentially life-threatening fungal infections. Its mechanism of action involves binding to ergosterol, a vital component of the fungal cell membrane, leading to the formation of pores and leakage of intracellular components, ultimately causing fungal cell death. 
• amphotericin B is effective against a wide range of fungi, including Aspergillus, Candida, Cryptococcus, Histoplasma, Blastomyces, Coccidioides, and several other species that can cause serious infections. However, it is ineffective against all types of fungi, and some species may resist the drug 
• In addition to its antifungal activity, amphotericin B has some antiviral and antibacterial effects, although it is primarily used as an antifungal agent 
• Cosmetic procedures: lidocaine topical can numb the skin before cosmetic procedures, such as Botox injections, dermal fillers, and chemical peels. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Chills 

Fever 

Hypokalemia 

Hypotension 

Nausea 

Pain (generalized) 

Renal function abnormalities 

Tachypnea 

Anorexia 

Diarrhea 

Headache 

Hypomagnesemia 

Malaise 

Pain at injection site 

Vomiting  

1-10% 

Delerium 

Hypertension 

Lumbar nerve pain 

Urinary retention 

Arachnoiditis 

Flushing 

Leukocytosis 

Paresthesia  

<1% 

Anuria 

Cardiac arrest 

Convulsions 

Hearing loss 

Maculopapular rash 

Thrombocytopenia 

Agranulocytosis 

Bone marrow suppression 

Coagulation defects 

Dyspnea 

Leukopenia 

Renal failure 

Vision changes 

Black Box Warning

Black box warning: 

The black box warning for amphotericin B highlights the risk of severe and potentially life-threatening side effects, including kidney damage, infusion reactions, and severe allergic reactions. These side effects can occur at any time during treatment with amphotericin B 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: amphotericin B should not be used in patients with known hypersensitivity or allergy to the drug. 
• Severe electrolyte imbalances: Patients with severe and deficient potassium or magnesium levels should not receive amphotericin B as it can further exacerbate these imbalances. 
• Renal impairment: Patients with severe renal impairment should not receive amphotericin B due to the risk of nephrotoxicity. 
• Pregnancy: amphotericin B is not recommended during pregnancy as it can harm a developing fetus. 
• Breastfeeding: It is not known whether amphotericin B is excreted in breast milk, so breastfeeding is not recommended while taking the medication. 

Caution: 

• Nephrotoxicity: amphotericin B can cause damage to the kidneys, particularly with prolonged or high-dose therapy. Patients receiving the medication should have their kidney function monitored regularly. 
• Electrolyte imbalances: amphotericin B can cause imbalances in electrolytes, such as potassium and magnesium, leading to cardiac and neuromuscular complications. Patients should have their electrolyte levels monitored during treatment. 
• Infusion-related reactions: amphotericin B can cause infusion-related reactions, such as fever, chills, nausea, vomiting, and headache. These reactions are more familiar with the first dose and can be managed with premedication and slowing the infusion rate. 
• Hepatotoxicity: In rare cases, amphotericin B can cause liver damage. Patients should have their liver function monitored during treatment. 
• Drug interactions: amphotericin B can interact with other medications, including diuretics and other nephrotoxic drugs.  
• Pregnancy and breast-feeding: amphotericin B can harm a developing fetus and is not recommended during pregnancy. It is also unknown whether the drug is excreted in breast milk, so breastfeeding is not recommended while taking amphotericin B. 

Pregnancy / Lactation

Pregnancy consideration: 

amphotericin B can harm a developing fetus and is not recommended during pregnancy 

Pregnancy category: B 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• amphotericin B is a broad-spectrum antifungal agent used to treat various systemic fungal infections, including candidiasis, aspergillosis, and cryptococcosis. It works by binding to ergosterol, a vital component of the fungal cell membrane, which causes the membrane to become more permeable and ultimately leads to the death of the fungal cell. 

• amphotericin B is available in several formulations, including conventional amphotericin B deoxycholate (Fungizone), lipid-based formulations such as liposomal amphotericin B (AmBisome), and lipid complexed amphotericin B (Abelcet). Lipid-based amphotericin B formulations are less toxic and more effective than conventional amphotericin B deoxycholate. 

Pharmacodynamics: 

The pharmacodynamics of amphotericin B involve its mechanism of action and the relationship between its concentration and the response it produces. 

Mechanism of action: 

amphotericin B binds to ergosterol, a key component of fungal cell membranes, and forms pores in the membrane. This causes leakage of intracellular ions and molecules, leading to cell death. The drug also binds to cholesterol in human cell membranes but with a much lower affinity than ergosterol, which is why it has a higher specificity for fungal cells. 

Concentration-response relationship: 

The concentration of amphotericin B in the bloodstream and tissues is directly related to its antifungal activity. However, a narrow therapeutic window exists between the concentration required for efficacy and the concentration that produces toxicity.

The minimum inhibitory concentration (MIC) of amphotericin B varies among different fungi, and the dose required to achieve therapeutic concentrations can vary depending on the patient’s clinical condition and the site of infection. 

Time-dependent killing: 

amphotericin B exhibits time-dependent killing, meaning its efficacy depends on the duration of exposure to the drug. Therefore, it is usually administered once daily or every other day to achieve the optimal antifungal activity. 

Synergistic activity: 

amphotericin B has exhibited synergistic activity with other antifungal agents, such as flucytosine, azoles, and echinocandins. This can result in increased efficacy and a broader spectrum of activity against different types of fungi. 

Overall, the pharmacodynamics of amphotericin B involves its ability to bind to ergosterol in fungal cell membranes, its concentration-dependent antifungal activity, time-dependent killing, and synergistic activity with other antifungal agents.

The drug’s pharmacodynamics is critical to its therapeutic efficacy and toxicity profile, and careful dosing and monitoring are necessary to optimize its use in clinical practice. 

Pharmacokinetics: 

Absorption 

amphotericin B is not absorbed orally and must be administered intravenously. The absorption rate after intravenous administration depends on the formulation used, with conventional amphotericin B deoxycholate having a slower absorption rate than lipid-based formulations.  

Distribution 

amphotericin B has a large volume of distribution and is widely distributed throughout the body, including to tissues and organs such as the liver, spleen, and kidneys. The drug does not cross the blood-brain barrier well but can penetrate cerebrospinal fluid when given intrathecally.  

Metabolism 

amphotericin B is not metabolized by the liver or other organs. It acts as a non-specific ionophore, forming pores in the fungal cell membrane and leading to fungal cell death. 

Elimination and Excretion 

amphotericin B is eliminated primarily by the kidneys, with about 80% of the dose excreted unchanged in the urine. Renal impairment can lead to increased drug accumulation and toxicity, and dosage adjustments are necessary for patients with impaired renal function. 

Adminstartion

Administration: 

amphotericin B is available in several formulations, including conventional amphotericin B deoxycholate, lipid-based formulations such as liposomal amphotericin B, and lipid-complexed amphotericin B. The administration of amphotericin B depends on the formulation used and the type of fungal infection being treated.  

Conventional amphotericin B deoxycholate: 

Conventional amphotericin B is usually administered intravenously at a dose of 0.3-1.0 mg/kg/day, depending on the patient’s clinical condition and the severity of the infection. The infusion is usually given over 2-6 hours, with the infusion rate gradually increasing over time to minimize the risk of infusion-related reactions. The drug is given daily or every other day, depending on the patient’s response.  

Liposomal amphotericin B: 

Liposomal amphotericin B is usually administered intravenously at a dose of 3-5 mg/kg/day, depending on the patient’s clinical condition and the severity of the infection. The infusion is usually given over 2-4 hours, with the infusion rate gradually increasing over time to minimize the risk of infusion-related reactions. The drug is given daily or every other day, depending on the patient’s response.  

Lipid complexed amphotericin B: 

Lipid complex amphotericin B is usually administered intravenously at a dose of 5 mg/kg/day, depending on the patient’s clinical condition and the severity of the infection. The infusion is usually given over 2-4 hours, with the infusion rate gradually increasing over time to minimize the risk of infusion-related reactions. The drug is given daily or every other day, depending on the patient’s response.  

Intrathecal administration: 

Intrathecal administration of amphotericin B may be considered in patients with fungal meningitis. The drug is usually administered at a dose of 0.1-0.5 mg/day, depending on the patient’s clinical condition and the severity of the infection. Intrathecal administration of amphotericin B carries a risk of neurotoxicity and should only be done by experienced clinicians. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: amphotericin B deoxycholate 

Why do we use amphotericin B? 

amphotericin B is an antifungal medication used to treat various fungal infections, including systemic fungal infections that are life-threatening or have a high risk of dissemination. Here are some of the common uses of amphotericin B: 

• Invasive aspergillosis: amphotericin B is considered a first-line treatment for invasive aspergillosis, a severe fungal infection that can affect immunocompromised patients. 
• Candidiasis: amphotericin B treats systemic candidiasis, a fungal infection caused by Candida species. It may also treat other forms of candidiasis, such as esophageal or urinary tract infections. 
• Cryptococcal meningitis: amphotericin B is used to treat cryptococcal meningitis, a fungal infection of the membranes surrounding the brain and spinal cord. 
• Mucormycosis: amphotericin B is used to treat mucormycosis, a rare but serious fungal infection that can affect immunocompromised patients. 
• Histoplasmosis: amphotericin B may be used to treat severe cases of histoplasmosis, a fungal infection caused by Histoplasma capsulatum. 
• Blastomycosis: amphotericin B may be used to treat severe cases of blastomycosis, a fungal infection caused by Blastomyces dermatitidis. 
• Coccidioidomycosis: amphotericin B may be used to treat severe cases of coccidioidomycosis, a fungal infection caused by Coccidioides immitis or Coccidioides posadasii.